Asthma pharmacology

Question 1

What type of respiratory disorder is asthma?

Answer 1

Obstructive

Question 2

Signs and symptoms of asthma?

Answer 2

Dyspnoea, a feeling of breathlessness

A wheeze, particularly on exhalation (and sometimes heard only on exhalation)

A cough, usually dry, but sometimes productive of thin mucous threads towards the end of an attack

Palpitation or tachycardia

Light-headedness or feeling faint

In moderate to severe asthma (which is not common), you might also see:

Tiredness or drowsiness

Cyanosis

Question 3

What is allergic asthma?

Answer 3

Acute attacks are triggered by exposure to an allergen, and the attack resolves when the allergen is removed.

Question 4

In mild to moderate asthma, the airway obstruction is caused by which two factors?

Answer 4

Oedema of the airway walls, narrowing the lumen

Mucus in the airway lumen (both of these features result from the acute inflammatory process in the lungs that is part of an acute asthma attack).

Question 5

Why does an asthmatic become alkalaemic early on?

Answer 5

Mucus early on is very watery, so carbon dioxide dissolves in it easily.

The patient is hyperventilating because of the asthma, and so carbon dioxide is blown off: the blood CO2 levels fall below normal, and the pH rises.

Patients are alkalaemic at this stage

Question 6

What happens to mucous if the attack progresses past an acute stage? Why?

Answer 6

Mucus becomes more viscid and less aqueous (as a result of sympathetic stimulation, and perhaps also of dehydration caused by the earlier hyperventilation)

Question 7

Why does an asthmatic become acidaemic as their attack progresses?

Answer 7

More viscous mucous

Carbon dioxide dissolves in it much less easily, and so the patient begins to retain CO2 and becomes acidaemic.

Question 8

Why is the cause of breathlessness?

Answer 8

Receptors in the lungs detect the distortion of pulmonary tissue caused by the oedema, and that signal to the central nervous system, resulting in an increased ventilatory effort.

Question 9

Does hypoxaemia cause breathlessness?

Answer 9

No, only in very late stages

Question 10

What triggers allergic asthma?

Answer 10

Hypersensitivity reaction.

An allergen triggers a response when it binds to IgE; the bound IgE triggers activation of mast cells in the bronchial epithelium; and histamine is released to start the acute inflammatory process.

Question 11

What leukocytes are activated and recruited in asthma?

Answer 11

Eosinophils

Question 12

What T cells recruit eosinophils?

Answer 12

Th2

Question 13

What effects to stimulated eosinophils have?

Answer 13

Release proteases and perforins, and can cause widespread damage to host tissues

Degranulate very easily

Question 14

What cytokines may commonly trigger eosinophil activation?

Answer 14

IL-5, IL-13

Question 15

What are two approaches to asthma treatment?

Answer 15

Symptomatic treatments

Disease modifying drugs

Question 16

What is a common short acting sympathetic agonist?

Answer 16

Salbutamol

Question 17

How to sympathetic agonists work?

Answer 17

Bind beta-2 leading to bronchodilation

Question 18

What is a common long acting sympathetic agonist?

Answer 18

Salmeterol

Question 19

Why is salmeterol used?

Answer 19

Useful in patients who need salbutamol often: for example, a common indication is in people who often wake in the night needing salbutamol inhalers: a long-acting agonist can offer an uninterrupted night’s sleep for such patients.

Question 20

What is an alternative type of sympathetic agonist?

Answer 20

Aminophylline (a methylxanthine) inhibitor of phosphodiesterase type III - raises cAMP to amplify any beta-adrenergic stimulation.

Question 21

How to parasympathetic antagonists work?

Answer 21

Muscarinic antagonists are an alternative approach to sympathomimetics

Question 22

What is a short acting parasympathetic antagonist?

Answer 22

Ipratropium (a derivative of atropine): short-acting, given by inhaler,

Question 23

What is a long acting parasympathetic antagonist?

Answer 23

Tiotropium long-acting, less commonly used

Question 24

What are two ways to give steroids, why give them either way?

Answer 24

Inhaled (e.g. beclomethasone), for mild to moderate asthma and Oral, for severe asthma

Question 25

Steroid side effects

Answer 25

Altered metabolism, including hyperglycaemia, mood swings, fluid retention (actually sodium retention), hypertension, thrombosis, osteoporosis

Question 26

How to minimise steroid side effects

Answer 26

Administer steroids by inhaler, rather than orally (systemically), whenever possible

Review dose regularly to ensure that the dose is kept to the minimum needed for control of the asthma

Question 27

What are prostaglandins and leukotrienes derived from?

Answer 27

Arachidonic acid

Question 28

What is arachidonic acid derived from?

Answer 28

Either diacylglycerol or the phospholipids found in cell membranes.

Question 29

What are the most important eicosanoid in asthma?

Answer 29

Leukotrienes – a mixture of leukotrienes C4, D4 and E4.

Question 30

How do corticosteroids work?

Answer 30

Inhibit the synthesis and action of the enzyme phospholipase A2, which cleaves arachidonic acid and is therefore key to the synthesis of both prostaglandins and leukotrienes.

Can also suppress transcription of many of the cytokine signals involved in acute inflammation.

Question 31

Leukotriene antagonists work by

Answer 31

Specifically suppressing the production of leukotrienes: unlike corticosteroids, they do not affect the production of prostaglandins and they do not usually affect the transcription of cytokines.

Question 32

What is a leukotriene antagonist?

Answer 32

Zafirlukast

Question 33

How do monoclonal antibodies act?

Answer 33

Suppression of the cytokine signals that are particularly associated with eosinophilic activity

Question 34

What cytokines are targeted in monoclonal therapy?

Answer 34

IL-5
IL-13
IgE (Omalizumab)
IL-6

Question 35

Clinical treatment for mild intrinsic asthma?

Answer 35

Short-acting bronchodilator with no other drugs (but with advice about possible lifestyle changes). In this case salbutamol is the most common choice, with ipratropium used in patients who cannot tolerate salbutamol.

Question 36

Clinical treatment for mild to moderate asthma?

Answer 36

If indication of a chronic inflammatory component inhaled steroids as their primary therapy, with salbutamol inhaler as treatment for occasional acute asthma attacks

When salbutamol fails: inhaled steroids, as before, with ipratropium as treatment for acute attacks

Question 37

Clinical treatment for moderately severe asthma?

Answer 37

Increase the dose of inhaled steroids, and step after that is to switch to oral steroids, to achieve a wider systemic immunosuppression.

Question 38

Clinical treatment when oral steroids leave patient still symptomatic?

Answer 38

Candidate for monoclonal antibody therapy, to try to achieve a more complete but more specific immunosuppression